The optimal line for HER2-targeted therapy could depend upon their toxicity profile, Eleftherios Mamounas, MD, suggests. As more therapies gain approval, they could be sequenced based on their toxicity profile, since each has similar efficacy. With this strategy, T-DM1 would be utilized upfront, followed by trastuzumab and anthracyclines, Mamounas believes.

Other studies are assessing T-DM1 in the neoadjuvant and adjuvant setting, notes Hope S. Rugo, MD. The phase II ATEMPT trial is comparing adjuvant T-DM1 with trastuzumab and paclitaxel for women with HER2-positive breast cancer. The primary endpoint of the study is disease-free survival (DFS). In the neoadjuvant setting, T-DM1 plus pertuzumab was explored in the I-SPY2 trial, Rugo notes.

The ATEMPT trial was preceded by the APT study, which examined adjuvant trastuzumab with chemotherapy followed by trastuzumab alone. At a 3-year analysis of this study, the DFS rate was 98.7%. If T-DM1 shows similar results, it will likely be used preferentially in the adjuvant setting, Adam Brufsky, MD, PhD, suggests. However, Rugo believes a clear clinical benefit is needed to begin using adjuvant T-DM1, since trastuzumab can be administered using methods that ameliorate the side effects to a level that is similar to T-DM1.